Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
November-2023 Volume 50 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
November-2023 Volume 50 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML

  • Supplementary Files
    • Supplementary_Data.pdf
Article Open Access

RNA‑binding protein quaking 5 inhibits the progression of non‑small cell lung cancer by upregulating netrin‑4 expression

  • Authors:
    • Zhuo Wu
    • Shijun Liu
    • Geshuo Pang
    • Hongfang Jiang
  • View Affiliations / Copyright

    Affiliations: Department of Thoracic Surgery, Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, P.R. China, Department of Geriatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
    Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 204
    |
    Published online on: October 3, 2023
       https://doi.org/10.3892/or.2023.8641
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

It was recently reported that netrin‑4 (Ntn‑4), a component of the extracellular matrix, when downregulated, is involved in the progression of several types of cancer, including breast cancer, colorectal tumours, neuroblastoma and gastric cancer. In the present study, the level of Ntn‑4 was examined in a public non‑small cell lung cancer (NSCLC) dataset from the Netherlands Cancer Institute. This analysis revealed that the mRNA expression level of Ntn‑4 was lower in the samples of patients with NSCLC compared with that in the control samples. Consistent with the mRNA level, the protein level of Ntn‑4 was also found to be decreased in NSCLC cells. However, both the function of Ntn‑4 and the underlying mechanisms of Ntn‑4 downregulation in NSCLC have yet to be fully elucidated. As was anticipated, the overexpression of Ntn‑4 led to a marked decrease in the proliferation, migration and invasion of NSCLC cells. Notably, RNA‑binding protein quaking 5 (Qki‑5) was found to exhibit antitumor activity in lung cancer, not only by enhancing the level of Ntn‑4 by binding to Ntn‑4 mRNA, but also by suppressing the proliferation, invasion and migration of NSCLC cells. However, Qki‑5 is known to be frequently downregulated in NSCLC. Moreover, the knockdown of Ntn‑4 was found to reverse the suppressive effects of Qki‑5 on NSCLC progression both in vitro and in vivo. Taken together, the findings of the present study demonstrate that Ntn‑4 is able to suppress the progression of NSCLC, and that the level of Ntn‑4 can be regulated by Qki‑5. Therefore, Ntn‑4 may be a novel diagnostic and therapeutic target for the treatment of NSCLC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Gazdar AF: Should we continue to use the term non-small-cell lung cancer? Ann Oncol. 21 (Suppl 7):vii225–vii229. 2010. View Article : Google Scholar : PubMed/NCBI

2 

Ellis PM and Vandermeer R: Delays in the diagnosis of lung cancer. J Thorac Dis. 3:183–188. 2011.PubMed/NCBI

3 

Cirulli V and Yebra M: Netrins: Beyond the brain. Nat Rev Mol Cell Biol. 8:296–306. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Yurchenco PD and Wadsworth WG: Assembly and tissue functions of early embryonic laminins and netrins. Curr Opin Cell Biol. 16:572–579. 2004. View Article : Google Scholar : PubMed/NCBI

5 

Bruikman CS, Zhang H, Kemper AM and van Gils JM: Netrin family: Role for protein isoforms in cancer. J Nucleic Acids. 2019:39471232019. View Article : Google Scholar : PubMed/NCBI

6 

Ziegon L and Schlegel M: Netrin-1: A modulator of macrophage driven acute and chronic inflammation. Int J Mol Sci. 23:2752021. View Article : Google Scholar : PubMed/NCBI

7 

Nacht M, St Martin TB, Byrne A, Klinger KW, Teicher BA, Madden SL and Jiang Y: Netrin-4 regulates angiogenic responses and tumor cell growth. Exp Cell Res. 315:784–794. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Eveno C, Broqueres-You D, Feron JG, Rampanou A, Tijeras-Raballand A, Ropert S, Leconte L, Levy BI and Pocard M: Netrin-4 delays colorectal cancer carcinomatosis by inhibiting tumor angiogenesis. Am J Pathol. 178:1861–1869. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Eveno C, Contreres JO, Hainaud P, Nemeth J, Dupuy E and Pocard M: Netrin-4 overexpression suppresses primary and metastatic colorectal tumor progression. Oncol Rep. 29:73–78. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Lejmi E, Leconte L, Pedron-Mazoyer S, Ropert S, Raoul W, Lavalette S, Bouras I, Feron JG, Maitre-Boube M, Assayag F, et al: Netrin-4 inhibits angiogenesis via binding to neogenin and recruitment of Unc5B. Proc Natl Acad Sci USA. 105:12491–12496. 2008. View Article : Google Scholar : PubMed/NCBI

11 

Lv B, Song C, Wu L, Zhang Q, Hou D, Chen P, Yu S, Wang Z, Chu Y, Zhang J, et al: Netrin-4 as a biomarker promotes cell proliferation and invasion in gastric cancer. Oncotarget. 6:9794–9806. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Villanueva AA, Falcon P, Espinoza N, R LS, Milla LA, Hernandez-SanMiguel E, Torres VA, Sanchez-Gomez P and Palma V: The Netrin-4/Neogenin-1 axis promotes neuroblastoma cell survival and migration. Oncotarget. 8:9767–9782. 2017. View Article : Google Scholar : PubMed/NCBI

13 

Reuten R, Patel TR, McDougall M, Rama N, Nikodemus D, Gibert B, Delcros JG, Prein C, Meier M, Metzger S, et al: Structural decoding of netrin-4 reveals a regulatory function towards mature basement membranes. Nat Commun. 7:135152016. View Article : Google Scholar : PubMed/NCBI

14 

Mehlen P and Fattet L: Netrin-4 regulates stiffness and metastasis. Nat Mater. 20:722–723. 2021. View Article : Google Scholar : PubMed/NCBI

15 

Reuten R, Zendehroud S, Nicolau M, Fleischhauer L, Laitala A, Kiderlen S, Nikodemus D, Wullkopf L, Nielsen SR, McNeilly S, et al: Basement membrane stiffness determines metastases formation. Nat Mater. 20:892–903. 2021. View Article : Google Scholar : PubMed/NCBI

16 

Esseghir S, Kennedy A, Seedhar P, Nerurkar A, Poulsom R, Reis-Filho JS and Isacke CM: Identification of NTN4, TRA1, and STC2 as prognostic markers in breast cancer in a screen for signal sequence encoding proteins. Clin Cancer Res. 13:3164–3173. 2007. View Article : Google Scholar : PubMed/NCBI

17 

Yi L, Lei Y, Yuan F, Tian C, Chai J and Gu M: NTN4 as a prognostic marker and a hallmark for immune infiltration in breast cancer. Sci Rep. 12:105672022. View Article : Google Scholar : PubMed/NCBI

18 

Chenard CA and Richard S: New implications for the QUAKING RNA binding protein in human disease. J Neurosci Res. 86:233–242. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Biedermann B, Hotz HR and Ciosk R: The Quaking family of RNA-binding proteins: Coordinators of the cell cycle and differentiation. Cell Cycle. 9:1929–1933. 2010. View Article : Google Scholar : PubMed/NCBI

20 

de Miguel FJ, Pajares MJ, Martinez-Terroba E, Ajona D, Morales X, Sharma RD, Pardo FJ, Rouzaut A, Rubio A, Montuenga LM and Pio R: A large-scale analysis of alternative splicing reveals a key role of QKI in lung cancer. Mol Oncol. 10:1437–1449. 2016. View Article : Google Scholar : PubMed/NCBI

21 

Zhang H, Li J, Tian F, Su X, Wang X, Tang D, Zhang L, Zhang T and Ni Y: QKI-6 suppresses cell proliferation, migration, and emt in non-small cell lung cancer. Front Oncol. 12:8975532022. View Article : Google Scholar : PubMed/NCBI

22 

Zhou X, Li X, Sun C, Shi C, Hua D, Yu L, Wen Y, Hua F, Wang Q, Zhou Q and Yu S: Quaking-5 suppresses aggressiveness of lung cancer cells through inhibiting β-catenin signaling pathway. Oncotarget. 8:82174–82184. 2017. View Article : Google Scholar : PubMed/NCBI

23 

Zhang B, Chen M, Jiang N, Shi K and Qian R: A regulatory circuit of circ-MTO1/miR-17/QKI-5 inhibits the proliferation of lung adenocarcinoma. Cancer Biol Ther. 20:1127–1135. 2019. View Article : Google Scholar : PubMed/NCBI

24 

Wang S, Tong X, Li C, Jin E, Su Z, Sun Z, Zhang W, Lei Z and Zhang HT: Quaking 5 suppresses TGF-β-induced EMT and cell invasion in lung adenocarcinoma. EMBO Rep. 22:e520792021. View Article : Google Scholar : PubMed/NCBI

25 

Wang JZ, Fu X, Fang Z, Liu H, Zong FY, Zhu H, Yu YF, Zhang XY, Wang SF, Huang Y and Hui J: QKI-5 regulates the alternative splicing of cytoskeletal gene ADD3 in lung cancer. J Mol Cell Biol. 13:347–360. 2021. View Article : Google Scholar : PubMed/NCBI

26 

Li N, Deng CL, Zhang B and Ye HQ: Viral titer quantification of west nile virus by immunostaining plaque assay. Methods Mol Biol. 2585:15–21. 2023. View Article : Google Scholar : PubMed/NCBI

27 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

28 

Coomer AO, Black F, Greystoke A, Munkley J and Elliott DJ: Alternative splicing in lung cancer. Biochim Biophys Acta Gene Regul Mech. 1862:1943882019. View Article : Google Scholar : PubMed/NCBI

29 

Sebestyen E, Zawisza M and Eyras E: Detection of recurrent alternative splicing switches in tumor samples reveals novel signatures of cancer. Nucleic Acids Res. 43:1345–1356. 2015. View Article : Google Scholar : PubMed/NCBI

30 

Staquicini FI, Dias-Neto E, Li J, Snyder EY, Sidman RL, Pasqualini R and Arap W: Discovery of a functional protein complex of netrin-4, laminin gamma1 chain, and integrin alpha6beta1 in mouse neural stem cells. Proc Natl Acad Sci USA. 106:2903–2908. 2009. View Article : Google Scholar : PubMed/NCBI

31 

Han Y, Shao Y, Liu T, Qu YL, Li W and Liu Z: Therapeutic effects of topical netrin-4 inhibits corneal neovascularization in alkali-burn rats. PLoS One. 10:e01229512015. View Article : Google Scholar : PubMed/NCBI

32 

Lee NG, Jeung IC, Heo SC, Song J, Kim W, Hwang B, Kwon MG, Kim YG, Lee J, Park JG, et al: Ischemia-induced Netrin-4 promotes neovascularization through endothelial progenitor cell activation via Unc-5 Netrin receptor B. FASEB J. 34:1231–1246. 2020. View Article : Google Scholar : PubMed/NCBI

33 

Dakouane-Giudicelli M, Brouillet S, Traboulsi W, Torre A, Vallat G, Si Nacer S, Vallée M, Feige JJ, Alfaidy N and de Mazancourt P: Inhibition of human placental endothelial cell proliferation and angiogenesis by netrin-4. Placenta. 36:1260–1265. 2015. View Article : Google Scholar : PubMed/NCBI

34 

Kociok N, Crespo-Garcia S, Liang Y, Klein SV, Nurnberg C, Reichhart N, Skosyrski S, Moritz E, Maier AK, Brunken WJ, et al: Lack of netrin-4 modulates pathologic neovascularization in the eye. Sci Rep. 6:188282016. View Article : Google Scholar : PubMed/NCBI

35 

Zhang H, Vreeken D, Leuning DG, Bruikman CS, Junaid A, Stam W, de Bruin RG, Sol WMPJ, Rabelink TJ, van den Berg BM, et al: Netrin-4 expression by human endothelial cells inhibits endothelial inflammation and senescence. Int J Biochem Cell Biol. 134:1059602021. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wu Z, Liu S, Pang G and Jiang H: RNA‑binding protein quaking 5 inhibits the progression of non‑small cell lung cancer by upregulating netrin‑4 expression. Oncol Rep 50: 204, 2023.
APA
Wu, Z., Liu, S., Pang, G., & Jiang, H. (2023). RNA‑binding protein quaking 5 inhibits the progression of non‑small cell lung cancer by upregulating netrin‑4 expression. Oncology Reports, 50, 204. https://doi.org/10.3892/or.2023.8641
MLA
Wu, Z., Liu, S., Pang, G., Jiang, H."RNA‑binding protein quaking 5 inhibits the progression of non‑small cell lung cancer by upregulating netrin‑4 expression". Oncology Reports 50.5 (2023): 204.
Chicago
Wu, Z., Liu, S., Pang, G., Jiang, H."RNA‑binding protein quaking 5 inhibits the progression of non‑small cell lung cancer by upregulating netrin‑4 expression". Oncology Reports 50, no. 5 (2023): 204. https://doi.org/10.3892/or.2023.8641
Copy and paste a formatted citation
x
Spandidos Publications style
Wu Z, Liu S, Pang G and Jiang H: RNA‑binding protein quaking 5 inhibits the progression of non‑small cell lung cancer by upregulating netrin‑4 expression. Oncol Rep 50: 204, 2023.
APA
Wu, Z., Liu, S., Pang, G., & Jiang, H. (2023). RNA‑binding protein quaking 5 inhibits the progression of non‑small cell lung cancer by upregulating netrin‑4 expression. Oncology Reports, 50, 204. https://doi.org/10.3892/or.2023.8641
MLA
Wu, Z., Liu, S., Pang, G., Jiang, H."RNA‑binding protein quaking 5 inhibits the progression of non‑small cell lung cancer by upregulating netrin‑4 expression". Oncology Reports 50.5 (2023): 204.
Chicago
Wu, Z., Liu, S., Pang, G., Jiang, H."RNA‑binding protein quaking 5 inhibits the progression of non‑small cell lung cancer by upregulating netrin‑4 expression". Oncology Reports 50, no. 5 (2023): 204. https://doi.org/10.3892/or.2023.8641
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team